DESCRIPTION: The broad, long-term objective of the proposed work is to understand the neural substrates of cortical multisensory processing, for it is these circuits that undoubtedly play an integral role in binding information from the different senses into a coherent perceptual whole. The emphasis of the previous grant period has been on detailing the development of multisensory cortical circuits and their plastic potential during early postnatal life, and we will continue to expand on this theme in the current work. In addition, we will focus on characterizing the functional circuitry that forms the basis for cortical multisensory processes, an essential yet unrealized step toward a better understanding of how our perceptual gestalt is created. The work will continue in the cat model, in which a substantial foundation of knowledge exists, facilitating the completion of the proposed studies. The work is divided into three specific aims. In the first, a combined anatomical and physiological approach will be employed in an effort to detail the functional architecture of cortical multisensory circuits. This work will represent the first systematic attempt to describe how multisensory networks in the cerebral cortex are assembled. In the second aim, the fine spatial architecture of cortical multisensory receptive fields will be detailed, and the hypothesis that receptive field structure and heterogeneity plays a critical deterministic role in multisensory interactions will be tested. These studies will be done in the awake and behaving animal in an effort to better understand the functional role of multisensory cortex. These experiments will seek to identify and describe a previously unrecognized level of complexity and flexibility to multisensory processes. In the final aim, the capacity of the adult brain for multisensory plasticity will be examined. Although it is clear from psychophysical studies that such capacity exists, virtually nothing is known about the neural substrates that likely form the basis for these changes. The ultimate goal of this work dovetails well with the mission of the National Institute of Mental Health (through whom this work has been previously funded), in that it seeks to further our basic science understanding of the brain bases of multisensory-mediated behavior and perception, with the ultimate goal of translating this knowledge into useful clinical strategies and interventions. In this regard, it is becoming increasingly clear that a number of clinical neurologic disorders with a sensory component (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, developmental dyslexia) may have preferential deficits in multisensory processing, and that both diagnostic and remediation strategies founded on a multisensory platform may provide more effective outcomes for individuals suffering with these conditions. PUBLIC HEALTH RELEVANCE The proposed work has great relevance in both the basic science and clinical arenas. An improved understanding of multisensory cortical processing is an essential step toward a more complete understanding of the brain bases of behavior and perception. Such knowledge will be of tremendous utility in the public health arena, in that it can be applied toward the development of more sensitive diagnostic tools, as well as more effective remediation strategies, in the fight against brain disorders such as autism and dyslexia in which sensory and multisensory processes are preferentially compromised. [unreadable] [unreadable] [unreadable]